The cerebral circulation is unique because it lies within a rigid structure, the cranium. Any increase in arterial inflow must be associated with a comparable increase in venous outflow because the intracranial contents cannot be compressed. The volume of blood and extravascular fluid can vary considerably in most body tissues. In the brain, however, the volume of blood and extravascular fluid is relatively constant; a change in one of these fluid volumes must be accompanied by a reciprocal change in the other. The rate of cerebral blood flow is maintained within a narrow range; in humans, it averages 55 mL/minute/100 g of brain tissue.
Regulation of Cerebral Blood Flow
At rest, the brain consumes 20% of total body oxygen and 25% of total body glucose. Of all body tissues, the brain is the least tolerant of ischemia. Interruption of cerebral blood flow for as little as 5 seconds results in loss of consciousness. Ischemia that lasts just a few minutes may cause irreversible tissue damage. Fortunately, regulation of the cerebral circulation is primarily under the direction of the brain itself. Local regulatory mechanisms and reflexes that originate in the brain tend to maintain a relatively constant cerebral circulation in the presence of such adverse effects as sympathetic vasomotor nerve activity, circulating humoral vasoactive agents, and changes in arterial blood pressure. Under certain conditions, the brain also regulates its blood flow by initiating changes in systemic blood pressure.
Changes in cerebral blood flow are associated with “functional recruitment” of capillaries. Thus the rate of flow through each capillary is adjusted to meet the needs of the organ. In “capillary recruitment,” in contrast, more capillaries are open to accommodate greater blood flow.
The brain has several protective mechanisms that regulate blood flow. These mechanisms include the blood-brain barrier, extrinsic regulation of central cardiovascular centers, intrinsic control (autoregulation) of circulation, and functional hyperemia, in which blood flow increases to a brain region that is active.
The blood-brain barrier regulates ion and nutrient transport between the blood and the brain and also limits the entry of harmful substances from the blood into the brain. The •Fig. 17.40 Diagram of a Neurovascular Unit With an Astrocyte Linking a Neuron to an Arteriole of the Brain Microcirculation.
Arteriolartoneismodulatedbyvascularsmoothmuscleandbytheactionofpericytes.Theendothelialcellrestrictsdiffusionofsubstancesbyvirtueoftightjunctions.Theneurovascularunitisacomponentoftheblood-brainbarrierandalsoservesasaregulatorofbloodflowduringneuronalactivity.
blood-brain barrier includes tight junction proteins (junctional adhesion molecule-1, occludins, claudins), which are connected to the endothelial cell cytoskeleton to form a barrier that opposes paracellular movement of substances from blood to brain. In addition, the blood-brain barrier includes the neurovascular unit (microcirculation, pericytes, the extracellular matrix, astrocytes, and neurons;
Fig.
17.40 ). Pericytes regulate blood flow by adjusting vascular diameter, and they secrete angiopoetin, a growth factor that stimulates the expression of occludins in endothelial cells. Occludins are prominently expressed in brain endothelial cells, in contrast to their sparse distribution in nonneural endothelium. The neurovascular unit regulates blood flow and capillary permeability. Thus the neurovascular unit is involved in pathological states, including hypoxia, neurodegenerative diseases, and inflammation, that are characterized by dysfunction of the blood-brain barrier.